Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26360 | 79303;79304;79305 | chr2:178567054;178567053;178567052 | chr2:179431781;179431780;179431779 |
| N2AB | 24719 | 74380;74381;74382 | chr2:178567054;178567053;178567052 | chr2:179431781;179431780;179431779 |
| N2A | 23792 | 71599;71600;71601 | chr2:178567054;178567053;178567052 | chr2:179431781;179431780;179431779 |
| N2B | 17295 | 52108;52109;52110 | chr2:178567054;178567053;178567052 | chr2:179431781;179431780;179431779 |
| Novex-1 | 17420 | 52483;52484;52485 | chr2:178567054;178567053;178567052 | chr2:179431781;179431780;179431779 |
| Novex-2 | 17487 | 52684;52685;52686 | chr2:178567054;178567053;178567052 | chr2:179431781;179431780;179431779 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs889825410  |
-1.685 | 1.0 | D | 0.824 | 0.65 | 0.767288954648 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 9.68E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs889825410 |
-1.685 | 1.0 | D | 0.824 | 0.65 | 0.767288954648 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs889825410 |
-1.685 | 1.0 | D | 0.824 | 0.65 | 0.767288954648 | gnomAD-4.0.0 | 7.43779E-06 | None | None | None | None | N | None | 4.00812E-05 | 1.66767E-05 | None | 3.37883E-05 | 0 | None | 0 | 0 | 4.23867E-06 | 1.09803E-05 | 1.60159E-05 |
| R/H | rs761481924 |
-2.2 | 1.0 | D | 0.823 | 0.673 | 0.53865211836 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.9E-06 | 0 |
| R/H | rs761481924 |
-2.2 | 1.0 | D | 0.823 | 0.673 | 0.53865211836 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs761481924 |
-2.2 | 1.0 | D | 0.823 | 0.673 | 0.53865211836 | gnomAD-4.0.0 | 3.96677E-05 | None | None | None | None | N | None | 4.00802E-05 | 5.00317E-05 | None | 0 | 0 | None | 0 | 0 | 3.98429E-05 | 6.58762E-05 | 8.00846E-05 |
| R/L | None | None | 1.0 | N | 0.775 | 0.702 | 0.797168046658 | gnomAD-4.0.0 | 6.84289E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99564E-07 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9959 | likely_pathogenic | 0.9941 | pathogenic | -1.721 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| R/C | 0.8525 | likely_pathogenic | 0.814 | pathogenic | -1.671 | Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.53251254 | None | None | N |
| R/D | 0.999 | likely_pathogenic | 0.9988 | pathogenic | -1.076 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| R/E | 0.9886 | likely_pathogenic | 0.9847 | pathogenic | -0.865 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/F | 0.9978 | likely_pathogenic | 0.9967 | pathogenic | -0.751 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| R/G | 0.9908 | likely_pathogenic | 0.9872 | pathogenic | -2.043 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | D | 0.550363306 | None | None | N |
| R/H | 0.7157 | likely_pathogenic | 0.6847 | pathogenic | -1.913 | Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.550616795 | None | None | N |
| R/I | 0.9919 | likely_pathogenic | 0.9874 | pathogenic | -0.783 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| R/K | 0.7672 | likely_pathogenic | 0.7324 | pathogenic | -1.246 | Destabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/L | 0.9789 | likely_pathogenic | 0.973 | pathogenic | -0.783 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.519674977 | None | None | N |
| R/M | 0.994 | likely_pathogenic | 0.9907 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| R/N | 0.9952 | likely_pathogenic | 0.9944 | pathogenic | -1.373 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/P | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -1.086 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.56222659 | None | None | N |
| R/Q | 0.7512 | likely_pathogenic | 0.6936 | pathogenic | -1.087 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| R/S | 0.9943 | likely_pathogenic | 0.9929 | pathogenic | -2.054 | Highly Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.520569896 | None | None | N |
| R/T | 0.9954 | likely_pathogenic | 0.9938 | pathogenic | -1.654 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/V | 0.9931 | likely_pathogenic | 0.9897 | pathogenic | -1.086 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| R/W | 0.9534 | likely_pathogenic | 0.9405 | pathogenic | -0.444 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| R/Y | 0.9915 | likely_pathogenic | 0.9874 | pathogenic | -0.313 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.